IL-12 induces autophagy in human breast cancer cells through AMPK and the PI3K/Akt pathway

Interleukin-12 (IL-12) serves an important role in immune responses and antitumor activity. The study of the association between autophagy and cancer cells remains controversial. The present study aimed to investigate the effect of IL-12 on autophagy in the human breast cancer cell lines MDA-MB-231 and MCF-7, and the possible molecular mechanism. Breast cancer cells were treated with different concentrations of recombinant IL-12. The expression of the autophagy-associated protein microtubule-associated protein light chain 3 (LC3) was determined using western blot analysis, fluorescein isothiocyanate-labeled LC3 was detected using fluorescence microscopy and autophagosomes were examined using transmission electron microscopy. Alterations in the phosphatidylinositol 3-kinase/Rac-a serine/threonine protein kinase (PI3K/Akt) and 5'-AMP-activated protein kinase subunit beta-1 (AMPK) pathways, in addition to pathwayassoci-ated proteins, were detected using western blotting, following treatment with IL-12 and pretreatment with the PI3K/Akt activator insulin-like growth factor or the AMPK inhibitor compound C. It was observed that IL-12 was able to upregulate the expression of the autophagy-associated protein LC3 in a concentration-and time-dependent manner, and induce the formation of autophagosomes in the two cell lines, and that the above effects involved the inhibition of the PI3K/Akt signaling pathway and the activation of the AMPK signaling pathway.